The effect of coronary vasodilators on collateral blood flow to ischemic myocardium is being studied in several canine models to better understand the principles and mechanisms involved. We have found that collateral flow is not evenly distributed in the ischemic region, but rather is higher at the edge than the center; however, collateral flow near the edge of the ischemic region is difficult to measure because tissue samples contain variable amounts on non-ischemic myocardium with high flow. The effect of dipyridamole, a small vessel dilator, on collateral flow is model-dependent. If one coronary artery is ligated and the other arteries are normal, dipyridamole causes an increase in collateral flow, but if the arteries supplying collateral flow are mildly stenose, collateral flow decreases (i.e., a "coronary steal" occurs). The "steal" appears to be caused by decreased pressure in the coronary beds providing collateral flow and occurs only with small vessel type dilators as opposed to large vessel dilators like nitrates. In a conscious dog model, inhibition of prostaglandin synthesis by indomethocin prevents the early increase in collateral flow that is normally seen and causes a larger area of myocardial necrosis at two days. Studies are continuing in this model using prostaglandin E2 and other vasoactive agents.